New Antidepressant ALKS 5461 Trials: 2016 Expected Availability

ALKS-5461 is a new drug that is being developed by the company Alkermes as an alternative to SSRI’s for the treatment of depression. ALKS-5461 (its trial name) is a combination of both buprenorphine (suboxone) and samidorphan, and is regarded as a non-addictive opioid modulator and antidepressant. It is currently being developed specifically as an antidepressant augmentation strategy in cases of treatment-resistant depression.

This drug is also being developed with the intention of treating cocaine dependence, and Alkermes has received a grant from the National Institute on Drug Abuse (NIDA) for the drug’s development. Initial research suggests that the drug produces a powerful antidepressant response within a week of treatment, in nearly everyone that takes it. Additionally the side effect profile appears to be relatively minimal.

What is ALKS-5461? The specific components.

ALKS-5461 is made up of both buprenorphine and samidorphan. These drugs work by influencing opioid receptor activity in the brain.

Buprenorphine: The buprenorphine portion of the drug acts as a partial agonist of the mu-opioid receptor (MOR) as well as an antagonist of the kappa-opioid receptor (KOR). Although not specifically prescribed to treat depression, many have found that taking suboxone for depression works better than any antidepressant they’ve ever tried.

Samidorphan: The samidorphan acts as a selective antagonist of the mu-opioid receptor (MOR). This works to essentially block the buprenorphine from binding to the mu-receptor, while not affecting the kappa-receptor.

How does the antidepressant ALKS-5461 work?

The combination of Buprenorphine and Samidorphan results in selectively blocking kappa-opioid receptors, while the effects on the mu-opioid receptor are thought to be minimal or insignificant. In other words, the drug gets the buprenorphine to bind to the kappa receptor, but not the mu receptor, which would minimize any “euphoric high” that opioid addicts seek. This would negate any addictive potential of the drug, while still producing an antidepressant response.

So why block the kappa receptor? When the kappa-opioid receptor becomes activated, naturally occurring peptides called “dynorphins” are released. Some research suggests that dynorphin levels are elevated among people with depression. Therefore blocking the kappa receptor will result in dynorphin reductions and may yield an antidepressant-like response.

Although dynorphins are important in a person’s stress response, at high levels they block the release of glutamate. Blocking glutamate in the brain can prevent neuroplasticity, lead to poorer learning abilities, and can induce learned helplessness. Since ALKS-5461 would be blocking dynorphin, it is thought that glutamate would get released to increase hippocampal plasticity and thereby reversing learned helplessness.

Additionally, blocking dynorphin can improve signaling of dopamine, which could lead to further reductions in depressive symptoms as a result of stress. Many researchers believe that kappa-opioid receptor antagonists may be a valid treatment option for both depression and anxiety in the future. In animal studies with kappa-opioid receptor antagonists, significant improvements in depression, anxiety, anhedonia, drug addiction, and stress-related behaviors has been shown.

Why aren’t there already kappa-opioid receptor antagonists on the market? In part because it’s difficult to develop this type of drug that provides favorable pharmacokinetic properties that isn’t toxic. Drugs need to be tested in regards to absorption, distribution, side effects, as well as efficacy. This seems to be the first drug of its type aimed at treating depression in humans.

So why not just use buprenorphine for depression?

Some people do use buprenorphine by itself as an off-label treatment for depression. Usually though, a person must have a history of opiate abuse in order to get a prescription. There have been cases where people have faked opiate addiction just to get buprenorphine for treatment-resistant depression; in many of these cases the individuals being treated were immediately relieved of depressive symptoms.

Although buprenorphine can work for depression, its activity on the mu-opioid receptor raises concerns over potential for both abuse and dependence. Additionally, it is thought that withdrawal from buprenorphine is relatively severe compared to other treatment options. Therefore, by combining samidorphan as seen in the drug ALKS-5461, it is theoretically removing the abusive potential of the buprenorphine.

ALKS-5461 Clinical Trials: Phase III To Finish in 2016

This drug already has undergone Phase II clinical trials and yielded very positive results. Due to the overwhelming positive response to the drug in trials, the FDA had granted “fast track designation” for treatment-resistant depression back in October 2013. As of June and July 2014, three major Phase III clinical trials were started in the United States.

The goal with the Phase III trials is to evaluate the efficacy of ALKS-5461 as a treatment strategy for individuals who don’t respond to modern day antidepressants in the SSRI and SNRI classes. If this drug is approved, it could treat depression from a different angle instead of relying on the hypothesis that low serotonin levels are to blame for feeling depressed.

Although the drug has been fast-tracked, it is still going to take a long time before results of the trials will be released. The trial results are likely going to come in 2016; a couple years from now. To supplement these trials, 9 smaller studies will also be done to finish up Phase III research. Assuming the drug ends up getting approval, this means we may be waiting a few more years before it hits the market.

The company Alkermes has already stated that they will be submitting a New Drug Application (NDA) to the FDA for the drug’s approve once Phase III research is complete. If the drug is approved, experts predict that the initial sales of the drug could be $25 million in 2016 and $350 million by 2019. The company also plans to out-license the drug, meaning they will collaborate with other companies for additional research, developments, and get a good initial return on the investment.

Phase I and Phase II Trial Results

In the first couple phases of clinical trials, ALKS-5461 was augmented with an SSRI or SNRI. Participants that received this drug experienced substantial improvement in treatment-resistant depression. In fact, most patients reported feeling significantly better within one week of supplementation. Up to half of all participants achieved complete remission in depressive symptoms. by the end of Phase I / II trials.

Another small trial that was conducted with a double-blind, placebo-controlled protocol demonstrated that 100% of people receiving the ALKS-5461 felt significantly less depressed. Although this was very small and only 32 people received the drug, these findings suggest that it works very quickly and very well. Many modern-day antidepressant treatments require weeks to generate a therapeutic response, whereas ALKS-5461 worked rapidly.

Comparison: Viibryd vs. ALKS-5461

A newer antidepressant on the market, Viibryd (Vilazodone) was approved by the FDA after multiple positive Phase III trials showing MADRS (Montgomery-Asberg Depression Rating Scale) decreases of 3.2 and 2.5 points in depressive symptoms. ALKS-5461 added to an SSRI and/or SNRI lead to MADRS decreases of 5.3 and 8.7 in Phase II trials. This demonstrates that people are responding between 2x and 3x better than they are while taking Viibryd as a standalone treatment.

What about ALKS-5461 side effects?

Based on research gathered from clinical trials, ALKS-5461 has been found to be pretty well-tolerated. Most common adverse effects include: nausea, vomiting, headaches, feeling sedated, and dizziness. The side effects seem to be relatively brief, affecting a person for a short duration when they begin taking the drug. With continuous usage, the nervous system adapts and most side effects completely disappear.

Final thoughts on ALKS-5461 for depression

We have known for years that opioids can improve mental health. Most people notice that they feel significantly more relaxed and experience mood improvement when they take an analgesic drug. Due to the fact that the market is largely saturated with SSRI and SNRI drugs that are associated with an array of unfavorable side effects including: sexual dysfunction and weight gain – companies are trying to come up with new options for treatment.

Personally, I am wondering why the drug is being used as an adjunctive treatment and not a standalone option. With improvements as cited in the study, why even waste time dealing with SSRI’s? Maybe the researchers are required to use it as an adjunct based on the fact that it is only for treatment-resistant or “refractory depression.”

Assuming it eventually gets approved for treatment of depression, I view it as a significantly safer option than taking something like an antipsychotic (e.g. Abilify). These days many doctors tack on an antipsychotic drug to an SSRI without realizing that the antipsychotic portion of the cocktail really has no business being used for depression.

When there’s a new breakthrough, it’s important to understand that this is not an “end all, be all.” Until the drug actually hits the market, we won’t really know how good or effective it is. In the meantime, we can hope other pharmaceutical companies begin to look at treatments other than targeting reuptake inhibition of serotonin as there are already enough of these drugs.

As a sufferer of major depression, I am frustrated that treatments like this weren’t researched years ago. At least it seems as though some progress is being made. If you are interested in being part of the clinical trial for this drug, it seems as though you must live in either Arizona or Georgia. Read the source below for further information.

Thank god there is new hope for sufferes of depression and anxiety in the form of ALKS 5461 – I’ve tried all the meds and none of them have worked. I have treatment resistant depression and GAD. The only drawback is we have to wait at least two years. I would understand if some brave people managed to get a prescription for buprenorphine, before then. Some of us are that desperate. Such a shame there are no clinic trials in the UK.

Rosie,
If you are suffering with treatment-resistent depression and anxiety and you want to try buprenorphine, you should go to an informed psychiatrist and ask for generic subutex. It is habit-forming, but not like the vicoden or percocet you’d get after surgery. It doesn’t create that euphoria. Many anxiety meds like Xanax are also addictive and you should avoid using those drugs or alcohol with buprenorphine.

Subutex is a sublingual buprenorphine tablet without naloxone. Please explain to the psych that you do not want to take the suboxone formulation with naloxone because of its effects on women, and you have no history of addiction or iv drug abuse. I suggest you start at a lose dose and take the minimum that helps you. Your dose will likely be 2mg per day, which I have seen otner women take long term in situations like yours. Will it give you tremendous relief? Probably. Is it right for you? That is your decision and your doctor’s.

To find doctors willing to prescribe suboxone & subutex, go to the website for suboxone (dot com) and then click find a doctor. You should find one in your area or nearby who is a psychiatrist. Not all of them are. Google their names until you find one who is. Even if you have to drive really far, I suggest you at least try it. Once you start treatment they may be willing to write 3 separate scripts at a time for you, dated each month, so you only need to see that psych every 3 months. You just give 1 script to the pharmacy each month and hold the others. Not every doctor is that flexible, but don’t be afraid to ask.

Many thanks for your reply – it’s a ray of hope for me. However I live in London England and I think you are saying to see a US psychiatrist? I googled subuxone (.com) and it didn’t seem to work – where do I go from here? Any ideas? Do you know of any psychiatrists in the UK who prescribe subutex for TRD? Thank you so much for your help, I think you understand the agony of clinical depression. God bless.

I believe I have drug resistant opiate induced depression. Tramadol helps with energy and mood enhancement for me in the past! Now I need opiates for pain and that has relieved the depression, but my energy levels aren’t as good as they are with tramadol due to the norepinephrine re-uptake inhibition! Just my two-cents! Good luck!

I hope they get ALKS-5461 to market ASAP because I believe that it can help depressed patients and it has relatively minor side effects and long-term health risk – unlike the anti-psychotics and other new drugs being ‘added to the cocktail.’ I am deeply disturbed by the inappropriate use of Abilify and even Topamax, for example.

I am not affiliated with this drug company, but I am a professional in the industry. I think the mechanism of action of ALKS-5461 is valid and should’ve been explored years ago. It’s no secret that opiates in low doses alleviate depression almost instantly. I’ve seen buprenorphine’s anti-depressant effects. Tramadol has also been noted for its anti-depressant properties and touted as non-addictive, since it’s not a true opiate analgesic yet still seems to cause similar effects in the brain.

But we all know opioids are addictive. I think the antidepressant action of opioids may be inextricably entangled with their addictive properties. Can ALKS-5461 really be a ‘free lunch’ in the neurochemical sense? I am skeptical that ALKS-5461 will be non-addictive. If I recall, the manufacturer of tramadol/ ultram made the same claim. It’s likely that the drug company developing ALKS-5461 knows it may be habit-forming, and that’s partly why they’re targeting it to treatment-resistent depression. In those hard cases, the risk of addiction is outweighed by potential benefit.

Would I prescribe it? Absolutely. To mature, adult depression sufferers with no history of alcoholism or drug abuse, who understand that no treatment is 100% free of side effects and are willing to accept the risk of dependency in exchange for a potential improvement in wellbeing.

I have known people who suffer from treatment resistant depression who intentionally developed a “opiate addiction” which doesn’t take long to do if done on a daily basis, just to be able to get a prescription for suboxone. They did their homework to ensure success. That is a sad situation when a person has to go to that extreme just to get relief from a legitimate and life threatening medical condition they never asked to be cursed with. If you suffer from treatment resistant depression you have no choice but to do whatever it takes to insure your survival.

Who WOULDN’T try it ? Unfortunately for some they don’t have the strength to make all that happen and are no longer with us because “it’s not prescribed for that”. If it ” was prescribed for that” they would probably still be alive. When it comes to your very survival you do what you have to do. If you leave it up to others you have to keep in mind, what do they have to lose if you live or you die? The truth be told ABSOLUTELY NOTHING!

Current mainstream psychiatry acts like ssri/snri not only are great for virtually all depressed patients, but even for other illnesses. It’s a charade. After 10 years of treatment resistance, I still kept running into doctors who acted like I’d never tried ssri or their cousins, without even checking my medical record which contains more than 10 of them. Almost half my life has now gone to waste due to anhedonia, lack of motivation and general emptiness, and it makes me furious to read about potential reliefs out there not even being tried, not even being on the radars.

You’d think trying off label meds should be part of the standard treatment protocol, as in with other medical conditions, and it’s not even like off label treatments are necessarily ‘less’ safe, there’s just a lot of stigma and generalizations out there. They even put patients through ECT and general anesthesia without even considering off label meds with long safety records.

In my humble opinion the key to long-term sobriety requires a great deal of “strength”, determination, tenacity, spirituality (not to be confused with Religion), patience and most importantly the ability to be brutally honest with oneself. Addiction stems from our desire to fill or numb ourselves of a painful, deep seeded “void” or emptiness in our soul (myself included).

This is nothing but another Big-Pharma scam… and any Doc worth his salt knows it. Buprenorphine (even with partial-bypassing the mu receptor to minimize any “euphoric high”) is still physically addictive, and physical withdrawal symptoms (though not as severe) can last as long or longer than methadone. People do well on Buprenorphine because it has such a long halflife (hence a month or two of withdrawals), it’s almost impossible to nod out on, and it eliminates withdrawals because your brain thinks it’s a derivative of the poppy (hence a month of withdrawals.)

ALKS 5461 will of course effectively treat symptoms of depression associated withdrawal because the individual will be getting their opiate fix. When that kappa receptor begins to feel lonely again when someone stops taking this drug they will be right back where they started, experiencing physical withdrawals and the nasty psychological demons associated with it. And to suggest that someone with a cocaine addiction swap over to an opioid addiction is pure insanity (unless you happen to be a Alkermes stockholder, which, I’m sure the authors of articles such as these must be.)

I’ve been an opiate addict for 14 years now (the last 7 of those I was taking methadone.) I’m going on my third year of suboxone treatment. I’m prescribed 24mg a day, but for the past 10 months I’ve tapered down to 4mg a day. 2mg when I wake up & 2mg around 6pm. Because of my impoverished state this past year the manufacturer pays for my prescription and I’m stockpiling the stuff because the withdrawals are physically tough and psychologically crippling.

I will concede that my quality of life has improved since Buprenorphine treatment. However, this may simply be because I no longer risk imprisonment to get what I need to get through the day. This is not some magic-bullet, but rather something this manufacturer knows it can sell a lot of for a long time, because if somebody stops taking it they’re going to hurt.

“Non-addictive opioid modulator” drew a raised eyebrow from me as well, but it’s a little bit more confusing than being a simple opiate drug like morphine or oxycodone.

Buprenorphine is a kappa-receptor ANTAGONIST, which is a reversal of opiate activity. Agonists of the kappa-receptor tend to cause dysphoria and confusion, substances like Salvia and various dissociatives. There is a lot of experimental basis for the function of the kappa-receptor in stress and anhedonia, so the idea is that blocking it would have beneficial effects for patients.

The kappa-receptor shows very low susceptibility for addiction in any case, it doesn’t cause the same opiate euphoria as the other opiate receptors. The mu-receptor is responsible for the addictive properties of narcotics and it would be blocked here by the samidorphan. I think it’s a little silly to use this combination instead of developing a pure kappa-receptor antagonist, but maybe that’s down the road if trials go well.

Awesome, awesome article! I have been telling people for about 2 years now that buprenorphine needs to be researched as an anti-depressant. My psychiatrist prescribes it to me at one (1!!!!!) mg a day for TRD and it has changed my life! (I was originally severely addicted to opiates/opioids and SSRIs/SNRIs wouldn’t touch my depression and I kept telling my GP that I don’t think my issue is serotonin/norepinephrine/dopamine related, but they kept giving me SSRI after SSRI until I had had enough and went to a Psychiatrist and told them the happiest I ever was was when I was taking buprenorphine for opiate addiction. But I didn’t want that high of a dose, showed him what all I had tried for depression/anxiety and “talked him in to” prescribing me 1 mg a day of buprenorphine and I am the happiest I have ever been. As the great Richard Gracer put it, “someone taking 0.5-1mg of buprenorphine for depression are no more addicted to it than someone taking Prozac.”

Your title relating to the potential availability of ALK-5461 is misleading. The trials are expected to wrap up in mid-2016. Even without delays, the company needs additional time to analyze the data and submit the NDA. Additional timeframes include the post-approval’s DEA classification decision, manufacturing and roll-out. So despite a fast track status, an FDA decision most likely won’t happen until at least sometime in 2017.

Well I would say that anyone reading this is mature enough to endure all the suffering we have experienced. I for one have had every type of med thrown at me and nothing has stuck. I as well think these new treatments should have been studied years ago. How many of us have lost loved ones or wake up in the ER not knowing how we got there? How many are in prisons or institutions that if spotted, their illness would be treated and they could live a productive life?

Joe, thanks for saying that. While reading this, my thoughts went to my Sister Jessie who killed herself in 2001 after a life long battle with TRD. Since her death, I have become involved with drugs and developed a heroin habit about 2 years ago. Luckily, I’m now enrolled in a research study for the Suboxone monthly injection.

I wish they didn’t take so damn long. I believe that Suboxone would have saved my sister’s life. I’m betting that it is going to save mine.

I took buprenorphine for “opiate addiction”, but really it was for depression. I was lucky enough to take Subutex, which is the mono formulation of buprenorphine WITHOUT naloxone in it and it works so much better than Subuxone, the mixed formulation. I was suffering from endogenous depression for a while, where I could say to myself, “there is literally no reason why I should be unhappy right now, but I still am”.

When I began taking buprenorohine, within a few days my outlook on life changed, my girlfriend said after three days of taking it, “I cannot believe how much you’ve changed”…all my close friends noticed it as well. There are plenty of studies you can search for where other opiates are used for depression as well, cases in which just 10mg of oxymorphone daily cured people with major depressive disorder where every other antidepressant and even electroshock failed.

I think it’s a sign of a pretty sick society where they’ll will try electrocution before giving you am opiate. In the end, if you do not commit crimes or do any other bad behavior, why can’t you just have what makes you happy? It’s obviously not about the side effects, because they’ll give you methadone or suboxone for the rest of your life, which will do the same amount of damage as any other opiate you might take, so what’s the difference?

One makes you “high”, or happy, which is just a stigmatized term anyway. Anyway, I think it’s insane when it’s claimed you’re in a free society, yet you cannot take a drug which improves your quality of life just because other people do not like the idea of it, seriously, it’s like there is this mass opinion where people just don’t want others to be happy unless it’s on the terms they decide.

What’s the worst that happens from me taking an opiate every day to be happy if I go to work and still take care of all my responsibilities? Any damage to my body is my choice, and should not be the concern of anyone else’s.

I’m excited about alks-5461. I’ve taken subutex (pure buprenorphine) for 18 months, initially to treat a codeine addiction. I currently take 1mg am & pm snapping a 2mg in half. The problem is that dosing Sub gives me a nice antidepressant effect and endorphin ‘bump’ for only 4 to 6 hours before anxiety, slight depression, and low mood/motivation kicks-in, despite the long half life of buprenorphine which takes care of physical side effects, but mental side effects appear short hours after dosing.

This could be due to kappa dynorphins being released even at a low dose like 1mg twice per day. I’ve gone as high as 16mg and the same outcome exists for me, a nice endorphin rush for several hours and then anxiety and a come-down. I tell my subutex Dr this & he just smiles or shrugs his shoulders. It works no better than codeine except perhaps a healthier option without the other toxic fillers.

I’m hoping alks-5461 will give me around the clock anti anxiety/depression relief but how hard it will be to convert and withdraw from subutex to alks-5461 I’m not sure.

I just wanted to mention to Kris that it is not well understood even by a lot of buprenorphine prescribers that while it has up to 30 hours of effectiveness to the mu receptor, all of us who are suffering from the co morbid depression/anxiety diagnosis need to be more conscious of its effect on the kappa receptor. For the kappa receptor buprenorphine lasts only about 4-6 hours. I don’t think whether you take 4 mg a day or 24 mg is as important as splitting your dose into 3-4 doses a day.

I’ve been on suboxone for almost five years now and up until about 9 months ago I was in a similar scenario where although the suboxone was a vital asset in originally assisting me with overcoming my active addiction. I was left with un-treated depression that was resistant to the ssri’s and other treatment options. I took my suboxone in the am and occasionally split it into two doses but had only minimal to moderate effectiveness on my depression.

As well, my dr kinda just shrugged his shoulders. Recently an addictionologist with a history of participating in medical research of buprenorphine educated me about the kappa receptors and splitting my dose into three to four doses a day vs just the once or twice has made a huge difference. I’d recommend giving that a try and if your on only like 2-4 mg a day possibly requesting to be increased to 8 mg just for ease of splitting it.

That small adjustment has honestly made a large difference in my mood, decreasing my apathy, and the physical and psychological pain associated with my depression. I admit to being one of those who does not look to taper off suboxone anytime soon. I do have some fear associated with the withdrawals of coming off. However, I’d just like to put out there that people on adderall or ritalin, etc. – all have varying degrees of physical and psychological addiction to their medications.

Most people being treated with these diagnoses, especially ADHD, are looking at life long pharmaceutical treatment. While I hope to have other factors such as exercise, meditation, group therapy be aspects of my treatment that hopefully lower my dependance on medications, I do not appreciate the stigma attached to the treatment of depression with medications affecting the opioid receptors. As someone who self medicated with OxyContin for eight years, I have a firm belief that my body and my depression is caused more prominently by effects of my Mu and koala receptors then necessarily serotonin and dopamine levels.

I have no desire to be hire or participate in the lifestyle associated with opiate use and active addiction. That doesn’t mean I’m not allowed to live a quality of life that allows me to be productive and happy because there is a stigma associated with any treatment regarding the opiod receptors. Un-educated people do not understand the great differences between methadone treatment which is a full agonist, and buprenorphine which works as a partial agonist.

The pharmacology of the two medications and physiological effects have different pathways and intended results as stated to some degree in the article. I agree it is unfortunate all of this research was not done fifteen or more years earlier. Finding a solution to the physical dependance associated with suboxone and subtext would be a great asset to producing a medication that successfully treats depression in a vastly different way then the ssri’s.

I also look forward to not having to participate in all the aspects of suboxone treatment that is usually associated with it such as having to be coded as opiod dependence, the monthly UA’s, required adjunct therapies such as seeing a Drug and alcohol abuse counselor, all which are expensive out of pocket and which five years later, having shown consistent commitment to living a clean lifestyle, I don’t believe I should have to continue with.

My dr agrees, treating me more as a mental health patient then as originally when I was seeking help for opioid dependance. However, we both have to “play the game” with current federal regulations and insurance policies regarding treatment. I look forward to any progress with these treatment options discussed in the article and the upcoming release to the public for treatment of depression.

For the first time in my life, I see the light. The darkness is gone. The loneliness has dissipated. I can get up, take care of my kids, graduate from college and hold a job… If there is a GOD, he will show people this light. My Life Finally Feels Worthwhile On Suboxone For Opiate Withdrawal!

UPDATE 20/10/2016. Alkermes plc (NASDAQ: ALKS) today announced positive topline results from FORWARD-5, the third phase 3 efficacy study to read out from the FORWARD pivotal program for ALKS 5461, a once-daily, oral investigational medicine with a novel mechanism of action for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies.

The study met its prespecified primary endpoint showing treatment with ALKS 5461 significantly reduced symptoms of depression in patients with MDD compared to placebo. ALKS 5461 was generally well tolerated. The most common adverse events observed for ALKS 5461 were nausea, dizziness and fatigue.

Based on these results, along with the substantial data collected to date on the efficacy and safety of ALKS 5461 for the treatment of MDD, the company plans to request a meeting with the U.S. Food and Drug Administration’s (FDA) Division of Psychiatric Products to discuss the filing strategy for this Fast Track designated medicine.

Thanks Angie for your information about the kappa receptor. To refresh other readers, I am perhaps in a minority of suboxone/subutex users that feels the need to dose it 3 or 4 times per day. I tell my prescribing doctor this and I’m written off as a hypochondriac. Of course a psychiatrist would understand that one or more of my other brain chemicals are suppressed; possibly dopamine, norepinephrine, or as Angie points out the kappa receptor does not stay saturated for very long despite buprenorphine’s long half life.

I firmly believe that genetically my brain doesn’t produce all of these chemicals as it should. I only have to look back on my childhood where I lacked laughter, high spirits and a real sense of enjoyment. Anyway, I have never been to a psychiatrist which in my view rules out hypochondria. I have dealt with my anxiety and depression with antidepressants prescribed by first line medical care.

To deal with the highs and lows of buprenorphine (suboxone/subutex) dosing I have discovered a “leveling out” by adding low dose venlafaxine (Effexor) or another dopamine booster (WS 5570) which is a patented St. John’s wort medication. But that’s not to say you should take these medications, please speak to your Dr first. But if you were only ever a codeine or other oral opiate dependent person (non H), don’t let your prescriber place you on really high amounts of Sub (>8mg).

Many will try to get you more dependent on this very strong opiate. Subs are a catch 22, it’s very strong on a mg basis, but yet only a partial opiate agonist. Sure if you have abused intravenous opiates then you may need 16 to 32mg per day. All I’m saying is that my experience as a sufferer of anxiety and depression, high mg Subs did not work for me. In fact I currently use 1mg of subutex 3 times per day and low dose Effexor (25mg twice daily).

But speak to your depression/anxiety Dr about which medication you could combine with it. As Angie pointed out from a conversation with an addictionologist, Subs may keep the mu receptor saturated for 24 hours, however the kappa may be short-lived at 4 to 6 hours. Or could it also be a dopamine problem? But I can only speak for myself, whether I dose 2mg or 24mg of Subs I get a very noticeable buzz for 4 to 6 hours and then a distinct come-down and edgy feel psychologically.

But again that’s just me… Angie does the Addiction Dr feel that it’s okay and healthy on the brain to do 4 low doses per day? I find multiple dosing works best for me as stated, but I must say I feel guilty sometimes because the so-called experts point out its a once daily medication. But I know that many people take subs twice per day. Thanks for reaching out.

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